1. Field of the Invention
The present invention relates to methods of identifying therapeutics useful for infectious diseases. More specifically, the present invention relates to methods of identifying antigens which are produced by infected cells, and the use of such antigens in immunogenic compositions or vaccines to treat or prevent infection.
2. Related Art
The immune system is the primary biological defense of the host (self) against potentially pernicious agents (non-self). These agents may be pathogens, such as bacteria or viruses, as well as modified self cells, including virus-infected cells, tumor cells or other abnormal cells of the host. Collectively, these targets of the immune system are referred to as antigens. The recognition of antigen by the immune system rapidly mobilizes immune mechanisms to destroy that antigen, thus preserving the sanctity of the host environment.
Antigens may provoke antibody-mediated responses and/or cell-mediated responses. Cells of the immune system termed B lymphocytes, or B cells, produce antibodies that specifically recognize and bind to the foreign substance. Other lymphocytes termed T lymphocytes, or T cells, both effect and regulate the cell-mediated response resulting eventually in the elimination of the antigen.
A variety of T cells are involved in the cell-mediated response. Some induce particular B cell clones to proliferate and to produce antibodies specific for the antigen. Others recognize and destroy cells that present foreign antigens on their surfaces. Certain T cells regulate the response by either stimulating or suppressing other cells.
Prospects for development of broadly effective tumor vaccines have been advanced by evidence that several self-proteins can be recognized as tumor antigens by immune T cells (Van den Eynde et al., J. Exp. Med. 173:1373 (1991); Bloom et al., J. Exp. Med. 185:453 (1997); Van Der Bruggen et al., Science 254:1643 (1991); Gaugler et al., J. Exp. Med. 179:921 (1994); Boel et al., Immunity 2:167 (1995); Van Den Eynde et al., J. Exp. Med. 182:689 (1995); Kawakami et al., Proc. Natl. Acad. Sci. U.S.A. 91:3515 (1994); Kawakami et al., Proc. Natl. Acad. Sci. U.S.A. 91:6458 (1994); Brichard et al., J. Exp. Med. 178:489 (1993)). Several genes and gene families that are expressed in melanoma and a fraction of tumors of other types but are silent in normal adult tissues except testis have been identified: MAGE-1 (van Der Bruggen, P., C. Traversari, P. Chomez, C. Lurguin, E. De Plaen, B. Van Den Eynde, A. Knuth, and T. Boon. 1991. Science 254: 1643–1647); MAGE-3 (Gaugler, B., B. Van den Eynde, P. van der Bruggen, P. Romero, J. J. Gaforio, E. De Plaen, B. Lethe, F. Brasseur, and T. Boon. 1994. J. Exp. Med. 179:921–930); BAGE (Boel, P., C. Wildman, M. L. Sensi, R. Brausseur, J. C. Renauld, P. Coulie, T. Boon and P. van der Bruggen. 1995. Immunity 2: 167–175); and GAGE (Van den Eynde, B., O. Peeters, O. De Backer, B. Gaugler, S. Lucas, and T. Boon. 1995. J. Exp. Med. 182: 689–698). In each case these gene products were identified by isolation of melanoma specific cytotoxic T cells from patients, and demonstration that the corresponding gene products are immunogenic.
Infected cells sometimes express self-proteins that are not expressed in uninfected cells. Geiss et al., Virology 266:8–16 (2000); Scheuring et al., AIDS 12:563–570 (1998).